Chromosomal instability is associated with higher expression of genes implicated in epithelial-mesenchymal transition, cancer invasiveness, and metastasis and with lower expression of genes involved in cell cycle checkpoints, DNA repair, and chromatin maintenance.
Chromosomal instability-a hallmark of epithelial cancers-is an ongoing process that results in aneuploidy and karyotypic heterogeneity of a cancer cell population. Previously, we stratified cancer cell lines in the NCI-60 drug discovery panel based on their karyotypic complexity and heterogeneity. Using this stratification in conjunction with drug response data for the cell lines allowed us to identify classes of chemical compounds whose growth-inhibitory activity correlates with karyotypic complexity and chromosomal instability. In this article, we asked the question: What are the biological processes, pathways, or genes associated with chromosomal instability of cancer cells? We found that increased instability of the chromosomal content in a cancer cell population, particularly, persistent gains and losses of chromosomes, is associated with elevated expression of genes involved with aggressive cellular behavior, including invasion- and metastasis-associated changes in cell communication, adhesion, motility, and migration. These same karyotypic features are negatively correlated with the expression of genes involved in cell cycle checkpoints, DNA repair, and chromatin maintenance.
Roschke
Anna V
AV
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889-5105, USA. roschkea@mail.nih.gov
Glebov
Oleg K
OK
Lababidi
Samir
S
Gehlhaus
Kristen S
KS
Weinstein
John N
JN
Kirsch
Ilan R
IR
D000704:Analysis of Variance; D002448:Cell Adhesion; D002450:Cell Communication; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000235:genetics; D030561:Databases, Nucleic Acid; D004847:Epithelial Cells; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007621:Karyotyping; D059630:Mesenchymal Stem Cells; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction